Findings That Cross Borders

Part of Regulatory Affairs and the Jurisdiction Map: Inspections and Regulatory Correspondence.

About 5 minutes. Free, in your language, no account needed.

Why this matters

A finding in one country is rarely confined to it, for two reasons that operate independently.

The first is factual. If a sponsor's process produced a defect in one country, the same process was almost certainly running everywhere else, and the defect is probably present there too. The finding is a sample, not an isolated event.

The second is institutional. Regulatory authorities communicate. Inspection outcomes are shared through established arrangements, and an authority may learn of another's finding before the sponsor tells it. Being asked about a finding you had not disclosed is a materially worse position than disclosing it.

The question to ask on the day a finding arrives

Not "how do we respond to this country?" That is the second question.

The first is: is the cause of this finding present anywhere else, and how would we know?

A finding that a site used an unapproved consent version raises the question of whether version control failed at that site or in the sponsor's distribution process. If it was distribution, every site is exposed. A finding that a safety report was late raises the question of whether the clock was misunderstood, in which case every report of that category in every jurisdiction using that clock is exposed.

This is the difference between correcting a finding and correcting a cause. An inspector who returns and sees the same finding in a different form knows immediately that the response addressed the symptom.

Scoping the assessment honestly

Once the cause is understood, the scope of exposure has to be assessed, and the temptation is to scope it narrowly.

Scope it by the cause. If the cause is a procedure, the scope is every study using that procedure. If the cause is a person's misunderstanding, the scope is everything that person did. If the cause is a system configuration, the scope is every study on that system.

Then state the scope you assessed and the scope you did not. "We have assessed the eleven studies using this procedure and found two further instances" is a strong statement. "We have no reason to believe this occurred elsewhere" is a weak one, and it is weak precisely because it describes an absence of investigation as though it were a finding.

Proactive disclosure

Where a finding in one country implicates conduct in another, disclosing it to the second authority before being asked is almost always the better course.

It is uncomfortable, and it is the position that survives. The sponsor that discloses is a sponsor with a functioning quality system that detected and reported a problem. The sponsor that waits is a sponsor that knew and did not say, and the second characterization attaches to everything else it says afterwards.

Where the framework requires disclosure, this is not a judgment call at all. Several jurisdictions require notification of serious breaches inside a defined period, and a finding by another authority can constitute knowledge that starts that clock.

In practice

An inspection in one country finds that safety letters were distributed to sites without acknowledgment being obtained, so the sponsor cannot evidence receipt.

The cause is not local. The distribution process is global and the same gap exists everywhere.

The regulatory lead's response has three parts, in this order. First, the corrective action in the inspected country, which is the part the authority asked for. Second, an assessment across all fourteen countries, which finds the same gap in all of them and quantifies it: 212 distributions over three years with no acknowledgment record. Third, a systemic fix with a date and a verification method.

She then discloses to the other thirteen authorities, describing the finding, the assessment, the scope, and the remediation.

Thirteen uncomfortable letters. What they buy is that when any of those authorities inspects, the sponsor's account of this problem is already on the record, dated before the inspection, with a remediation in progress. The alternative is the same finding discovered independently thirteen times, each time by a regulator who can see that the sponsor knew.

What this looks like when it goes wrong

A sponsor receives a finding in one country and fixes it there, thoroughly and well. The response is accepted and the matter closes.

Fourteen months later a different authority inspects a different study and finds the same defect, and asks whether the sponsor has encountered this before.

The honest answer is yes, in another country, fourteen months ago. The next question follows immediately and is the one with no good answer: what did the sponsor do to establish whether the problem existed here?

Nothing was done, because the finding was treated as a local matter closed by a local fix. The second finding is now not one finding. It is evidence that the sponsor's quality system does not propagate what it learns, which is a conclusion about the system rather than about a consent form or a safety letter.

Key takeaways